The dbl oncogene product contains a 238 amino acids domain (DH) which is shared by an expanding family of growth regulatory proteins. Recent studies have provided evidence that oncogenic dbl, or an associated protein, stimulates DGP dissociation from the human species (Hs) homolog of CDC42. The dbl oncogene specifically complexes with the GDP-bound forms of the small G-proteins, CDC42Hs and rhoA, but not rac1 or TC10. and that this specificity correlates with the ability of dbl to act as a GRF. Small deletions throughout the dbl domain which inactivate transformation. eliminate the ability of dbl to stimulate GDP dissociation; whereas deletions outside of this domain did not impair either function. Finally. the DH itself, as well as the whole dbl product. when expressed and purified as a recombinant protein was shown to stimulate DGP dissociation from purified, recombinant CDC42Hs. These findings demonstrate that dbl can act as a GRF for more than one rho-like protein and establish that the minimal unit on dbl that is critical to its transforming function also directly regulates its GDP-GTP exchange activity. In vitro and in vivo studies are being carried out in order to establish which dbl interactions with rho-like proteins are responsible for mediating their transforming function.